Levetiracetam (Keppra)

Another new anti-convulsant is being researched for bipolar disorder and mania.  No double-blind trials are available, although an interesting open trial with an ABA design was done by the University of Munich who wisely say that a double blind study is "required."

Three double-blind studies covering 904 patients have found levetiracetam effective for refractory partial epilepsy as an add-on medication averaging one year follow-up and 60% remaining on the medication (Int J Clin Pract. 2003 Sep;57(7):616-21).  It has been used in animal models of anxiety.  I have not located any human studies, although I saw a mention of such a study.

At least five cases of psychosis induced in children by levetiracetam have been reported (Epilepsia. 2001 Dec;42(12):1611-3).

It is definitely way too early to use levetiracetam in clinical practice.  Double-blind studies may find it to be an excellent medication.  I hope they will be done in the near future.

A Small On-Off-On Open Trial Reports Improvement While on Levetiracetam: 10 manic bipolar patients being treated with haloperidol 5-10 mg/d were given levetiracetam up to 4000 mg/d (average 3125) for the first 14 days, then no levetiracetam until day 21 when it was restarted. Mania YMRS scores decreased from 29.6 to 17.2 during the first "on" phase, manic symptoms worsened during the "off" period (YMRS score 20.9) and ameliorated again during the second "on" phase, with a decrease of the mean YMRS score to 14.7 at the end of the study. Researchers wisely say that controlled studies are "clearly required." Univ. Munich. Levetiracetam in the treatment of acute mania: an open add-on study with an on-off-on design. Grunze H, Langosch J, Born C, Schaub G, Walden J. J Clin Psychiatry. 2003 Jul;64(7):781-4. Ed: Hopefully, the researchers are doing a double-blind study.  My one concern is the language used in calling the 7 out of 10 patients who had a major improvement on levetiracetam "responders."  This term makes it sound like the study proved that levetiracetam was responsible for their improvement.  This would be incorrect.  Maybe all of the improvement was due to haloperidol and the passage of time and the deterioration was simply a withdrawal effect.  While I doubt that this is the case, even an On-Off-On open trial is not proof. 

Belgium Researchers Find Levetiracetam Helps Animal Model of Mania: Using a putative animal model for mania, namely, dexamphetamine-chlordiazepoxide mixture-induced hyperactivity in rats submitted to a Y-shaped maze test, the researchers tested levetiracetam vs. lithium chloride, sodium valproate, and carbamazepine as comparators. Effect of the New Antiepileptic Drug Levetiracetam in an Animal Model of Mania. Lamberty Y, Margineanu DG, Klitgaard H. Epilepsy Behav. 2001 Oct;2(5):454-459